SCCM Resource Library-Effects of Ketamine on Intracranial Pressure in Children With Severe Traumatic Brain Injury

Video Transcription

Hi, my name is Jennifer Laws, and today I will be presenting on the effects of ketamine on intracranial pressure in children with severe traumatic brain injury.  We wanted to start by reviewing the pharmacology and physiology of ketamine. Ketamine is an NMDA receptor antagonist and a glutamate receptor antagonist.  Because of its dissociative, anesthetic, and analgesic properties, it is commonly used as a sedative.  Ketamine does not have the negative hemodynamic consequences of other sedative agents, such as hypotension and bradycardia, because it blocks the reuptake of catecholamines.  This makes it appealing for use in critically ill patients in the ICU setting. Ketamine has traditionally been contraindicated for use in neurocritical care patients due  to concerns that it increases cerebral blood flow and thus increases intracranial pressure. Two studies from the 1970s supported this thought.  One compared ketamine use in adult patients with space-occupying lesions with those with normal CSF pathways.  This small study demonstrated an increase in intracranial pressure following ketamine administration in the group with space-occupying lesions, but did not see an increase in those  with normal CSF pathways. The second study saw an increase in ICP in healthy patients following ketamine administration.  Both of these studies did not account for the partial pressure of carbon dioxide, which we now know can impact cerebral blood flow.  Recently, adult studies have suggested the use of ketamine for adult TBI patients, including  two systematic reviews that demonstrated evidence that ketamine does not raise ICP in this patient population.  Some of the studies reviewed also revealed that CPP increased in their study patients following ketamine administration.  Two small adult studies found no significant increase in ICP when comparing ketamine with sufentanil or when comparing ketamine with fentanyl bolus and infusion.  Ketamine usage in TBI patients has also started to be studied in the pediatric population. One small prospective study looked at ketamine administrations in children with severe TBI  when ketamine was given for sustained ICP greater than 18 millimeters of mercury or when it was given as a pretreatment prior to a planned distressing event.  In this population, they observed that ICP did not increase following ketamine administration.  This study did not report the GCS of their patients, which limited the generalizability of their study.  The most recent pediatric severe TBI management guidelines acknowledge that there is evidence to suggest a reconsideration of ketamine use in pediatric severe TBI patients.  This evidence continues to be insufficient to provide a recommendation for this patient population.  Our pilot study aimed to observe the effect of ketamine on ICP in children with traumatic brain injury, both when ketamine was given as a sedative when ICP was not pathologically  elevated and also as an ICP-targeted therapy during sustained periods of intracranial hypertension.  We hypothesized that ketamine would not raise ICP when given as a sedative and also that ketamine could potentially lower ICP when used for the treatment of sustained intracranial  hypertension. We identified patients less than 18 years of age with traumatic brain injury who had ICP monitors in place.  These patients were treated in our intensive care unit via our severe traumatic brain injury treatment algorithm.  We used an automated data acquisition platform that recorded CPP and ICP from bedside monitors at one-minute intervals.  We noted drug administrations of sedatives, paralytics, hyperosmolar agents, and barbiturates that were synchronized with ICP and CPP recordings.  For each ketamine administration, ICP and CPP data was extracted for the five minutes before and the 120 minutes after each ketamine dose.  This ICP and CPP data was then averaged into different groups for further evaluation. For our patients who received ketamine during an ICP crisis, we defined an ICP crisis as  those who had an average ICP greater than 20 for the five minutes prior to the ketamine administration.  We also looked at medications given surrounding this ketamine administration and looked at the five minutes before and the 120 minutes after the ketamine dose.  We defined the end of an ICP crisis when the ICP was less than 20 for greater than five minutes.  After evaluating our raw data, we further censored our data to account for any medications given for a new ICP crisis.  In our censored data, any ICP or CPP data obtained following a subsequent medication dose for a new ICP crisis during the monitoring time period was censored.  We identified 35 patients with ICP monitors for traumatic brain injury. 33 of these patients had available ICP data to evaluate.  22 of those patients received ketamine during their monitoring period, and 11 of those patients received ketamine for ICP-targeted therapy.  We looked at high-frequency data from 33 pediatric traumatic brain injury patients and analyzed 127 doses of ketamine for 22 patients.  18 of those doses were given during ICP crises for 11 of the patients. These are our patient characteristics comparing those patients who received ketamine compared  to those who did not receive ketamine. We wanted to note that our Glasgow Coma Scleral Score for those who did not receive ketamine  was an average of 4 and was 5 for those who did receive ketamine. Here we present all of our ketamine administrations regardless of their baseline ICP.  We present the median ICP and CPP with the interquartile range in our graphs. From this data, we observed that in our patient population, there was no significant change  in ICP following administration of ketamine. Additionally, we did not see a significant change in CPP following ketamine administration as well.  This further separates our ketamine administrations to those patients who received ketamine for sedation during times when ICP was not elevated.  Again, we observed that there was no significant change from baseline in ICP or CPP following ketamine administration.  For our patient population who received ketamine during an ICP crisis, we saw a statistically  significant decrease in ICP from baseline at the 15-minute mark to the 120 minutes following ketamine administration.  When we censored our data to exclude medications given for additional episodes of ICP crises,  we saw no change in our findings, again, finding a statistically significant decrease in ICP following ketamine administrations at the same time intervals.  When we looked at CPP changes in our patients who received ketamine for ICP crises, we did  not find statistically significant changes in the CPP of our patients compared to baseline. This was either before or after censoring our data.  We then adjusted our CPP goals for their age-based norms and looked at change of CPP from baseline following ketamine administration.  We again did not find any statistically significant change in their age-based CPP values compared to baseline following ketamine.  We looked at the age, sex, and mechanism of injury for our patients who received ketamine for ICP crises.  We also looked at each ketamine dose separately to look at the characteristics of the specific ICP crises, as well as the bolus and continuous medications given during each crisis.  This is an example of a patient who received ketamine during an ICP crisis, and as you can see, they received their ketamine dose at the peak time of their ICP and had a subsequent  decrease in their ICP following ketamine. We also noted other medications that were given during this monitoring time period,  some that were given during times when ICP was not elevated. This is an example of a patient who received multiple ketamine boluses for a significant  ICP crisis that was refractory to many ICP-lowering medications. He was an eight-year-old male with traumatic brain injury after a motor vehicle collision  who had an admission GCS of 3T. He had a decompressive craniotomy, as well as a parenchymal ICP monitor placed on admission.  The ICP crisis that we're demonstrating occurred on hospital day five, and he had an EBD placed after this ICP crisis.  When he had multiple ketamine boluses given within five minutes of each other, we accounted them for a single dose, and we also noted other medications that was given during this  refractory ICP crises. He was ultimately discharged to inpatient rehabilitation on hospital day 31.  From our data, we did not find evidence to suggest that ICP increased from baseline following ketamine doses when given for sedation.  Additionally, when given in the setting of ICP crisis, ICP was found to decrease following ketamine administration.  One of our highlighted strengths of our study were that we were able to utilize higher frequency monitoring data, and we were also able to report the GCS of our patients.  Some of the limitations were that the timing of the doses were based on the scan time that was reported.  We were also unable to account for other ICP-lowering medications given to our patients, as well as multiple ketamine doses in each of our patients.  This small pilot study continues to add to data that questions the idea that ketamine should be avoided in patients with increased ICP, and in some situations may be useful  in treating ICP crises. Larger prospective studies are warranted to further evaluate the use of ketamine in this patient population.  I wanted to thank our research team, my pediatric program directors, as well as my pediatric co-chiefs, as well as the Surgical Outcomes Center for Kids for their support in this  project. I also wanted to thank the PICU and surgical teams who cared for these patients. Here are references that we used in this presentation. Thank you so much for listening.

Video Summary

In this presentation, Jennifer Laws discusses the effects of ketamine on intracranial pressure (ICP) in children with severe traumatic brain injury (TBI). Ketamine is commonly used as a sedative due to its dissociative, anesthetic, and analgesic properties. Traditionally, ketamine has been contraindicated for use in neurocritical care patients because it was believed to increase ICP. However, recent studies in adults have shown that ketamine does not raise ICP in TBI patients. Laws conducted a pilot study on pediatric TBI patients and found that ketamine did not raise ICP when given as a sedative and actually lowered ICP during periods of intracranial hypertension. Further research is required to evaluate the use of ketamine in this patient population.

Asset Subtitle

Neuroscience, Pharmacology, Pediatrics, 2022

Asset Caption

INTRODUCTION/HYPOTHESIS: Ketamine has traditionally been contraindicated in traumatic brain injury (TBI) because it is thought to raise intracranial pressure (ICP). However, more recent studies have challenged this. Also, current guidelines do not provide recommendations regarding ketamine in pediatric severe TBI. We used high-frequency monitor data to evaluate the effect of ketamine on ICP in children with severe TBI. We hypothesized that ketamine would not raise ICP and could potentially lower ICP when used in treatment of elevated ICP. METHODS: Data was retrospectively collected from ICP-monitored pediatric severe TBI patients treated at a quaternary care pediatric intensive care unit according to Brain Trauma Foundation guidelines, including treatment of ICP > 20mmHg for >5 minutes. Demographic and clinical data were recorded, including age, sex, admission Glasgow Coma Scale score, mechanism of injury, surgical decompression, and survival to discharge. Cerebral perfusion pressure (CPP) and ICP were recorded in an automated database at 1-minute intervals. Administration times of bolus medications for treatment of intracranial hypertension (3% saline, fentanyl, and ketamine) were synchronized with ICP and CPP recordings. ICP and CPP were compared each minute for 10 minutes after each ketamine administration, vs. baseline. For the subset of ketamine, 3% saline, and fentanyl doses given for ICP > 20mmHg for >5min, ICP and CPP were averaged into epochs ranging from -5 to 120 minutes from each dose and compared to baseline (-5 to 0 min). RESULTS: High-frequency data were obtained from 33 pediatric severe TBI patients. We analyzed 136 doses of ketamine in 22 patients. Of those, 10 doses were given for elevated ICP in 7 patients. ICP did not rise 1-10 minutes after ketamine doses. When given for ICP > 20mmHg, ICP was lower after ketamine doses (20-25 min, 16[14-21]; 25-30 min, 16[14-22]; 30-45 min, 15[14-20]; 45-60 min, 16[13-22]; 60-90min, 16[14-20]; 90-120min, 16[11-17] vs. -5-0 min, 25 [22-31]; median [IQR], Kruskal-Wallis, p < 0.05). CONCLUSIONS: In this pilot study, ketamine administration did not elevate ICP. When given for elevated ICP, we found preliminary evidence that ketamine may be associated with decreasing ICP. These findings warrant larger studies of ketamine’s effects on ICP in pediatric severe TBI.

Meta Tag

Content Type Presentation

Knowledge Area Neuroscience

Knowledge Area Pharmacology

Knowledge Area Pediatrics

Knowledge Level Advanced

Membership Level Select

Tag Traumatic Brain Injury TBI

Tag Analgesia and Sedation

Tag Pediatrics

Year 2022

Keywords

Jennifer Laws

ketamine

intracranial pressure

severe traumatic brain injury

pediatric TBI

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